Chemo-Enzymatic Cascade for the Generation of Fragrance Aldehydes

Round 1

Reviewer 1 Report

In the manuscript entitled “Chemo-enzymatic cascade for the generation of fragrance aldehydes” the authors report a general method to obtain aldehydes, useful for fragrance, by a chemo-enzymatic approach.

The article is interesting, but it is poor in details at paragraph 4. “Material and methods”. The authors have should report the chemical characterization of Heck’s reaction products and the final compounds obtained from enzymatic procedure. For this purpose the HPLC-MS analysis  for known cinnamic acid derivatives and for the final known aldehydes is enough, but better it would be to report the NMR and  MS data with relative spectra if available.

Please report in “Materials and Methods” the conditions used in HPLC analysis and add chromatograms for  1b-8b and 1d-8d in “Supplementary Material”, as well as, if NMR data are available insert it in “Material and Methods”  and any spectra  in Supplementary Material”.

At rows 39-41 it is reported :” Our aim was to exploit the unique chemoselectivities of reductive enzymes and to  explore routes for the generation of aromatic, chiral aldehydes via a chemoenzymatic reaction sequence”, as well as at row 72 is reported:” When the double bond of substituted cinnamaldehydes is reduced, a chiral center is generated”,  but nowhere in the manuscript is discussed the stereochemistry of obtained aldehydes. The compounds 2d, 4d, 6d and 8d are optically pure or are a mixture of enantiomers?  In this case, which is the enantiomeric excess?  Please discuss the stereochemistry of aldehydes with a chiral center.

In results and discussion at row 100-102 it is reported that acrolein and crotonaldehyde give a mixture of E and Z isomers. In which ratio? Please report the ratio in the text.

At row 117 it is written:” As reported previously, 1c tends to be reduced to the alcohol (1e)” please remove (1e) because it is cited but it is not present as structure in the text.

Author Response

A detailed reply can be seen in the attached p2p letter.

Author Response File: Author Response.pdf

Reviewer 2 Report

There are a few minor editorial corrections noted on the manuscript, these should be addressed. I was unable to determine the scale of the reactions from the manuscript, it would be nice to have a sense on what scale this could be effectively done on. Also, there is no discussion on the enantioselectivity of the overall process. Is it good, moderate or poor, would be important to know. It would be good to note for the reader how accessible these strains are and how easily this can be adapted into an organic research lab.

Comments for author File: Comments.pdf

Author Response

A detailed reply can be seen in the attached p2p letter.

Author Response File: Author Response.pdf